TY - JOUR

T1 - A metallothionein mimetic peptide protects neurons against kainic acid-induced excitotoxicity

AU - Sonn, Katrin

AU - Pankratova, Stanislava

AU - Korshunova, Irina

AU - Zharkovsky, Alexander

AU - Bock, Elisabeth

AU - Berezin, Vladimir

AU - Kiryushko, Darya

N1 - Keywords: Animals; Blood-Brain Barrier; Cells, Cultured; Cerebral Cortex; Disease Models, Animal; Dose-Response Relationship, Drug; Epilepsy, Temporal Lobe; Hippocampus; Kainic Acid; Male; Metallothionein; Mice; Mice, Inbred C57BL; Nerve Degeneration; Neuroprotective Agents; Neurotoxins; Peptides; Rats; Rats, Wistar; Seizures

PY - 2010

Y1 - 2010

N2 - Metallothioneins I and II (MTI/II) are metal-binding proteins overexpressed in response to brain injury. Recently, we have designed a peptide, termed EmtinB, which is modeled after the beta-domain of MT-II and mimics the biological effects of MTI/II in vitro. Here, we demonstrate the neuroprotective effect of EmtinB in the in vitro and in vivo models of kainic acid (KA)-induced neurotoxicity. We show that EmtinB passes the blood-brain barrier and is detectable in plasma for up to 24 hr. Treatment with EmtinB significantly attenuates seizures in C57BL/6J mice exposed to moderate (20 mg/kg) and high (30 mg/kg) KA doses and tends to decrease mortality induced by the high KA dose. Histopathological evaluation of hippocampal (CA3 and CA1) and cortical areas of mice treated with 20 mg/kg KA shows that EmtinB treatment reduces KA-induced neurodegeneration in the CA1 region. These findings establish EmtinB as a promising target for therapeutic development.

AB - Metallothioneins I and II (MTI/II) are metal-binding proteins overexpressed in response to brain injury. Recently, we have designed a peptide, termed EmtinB, which is modeled after the beta-domain of MT-II and mimics the biological effects of MTI/II in vitro. Here, we demonstrate the neuroprotective effect of EmtinB in the in vitro and in vivo models of kainic acid (KA)-induced neurotoxicity. We show that EmtinB passes the blood-brain barrier and is detectable in plasma for up to 24 hr. Treatment with EmtinB significantly attenuates seizures in C57BL/6J mice exposed to moderate (20 mg/kg) and high (30 mg/kg) KA doses and tends to decrease mortality induced by the high KA dose. Histopathological evaluation of hippocampal (CA3 and CA1) and cortical areas of mice treated with 20 mg/kg KA shows that EmtinB treatment reduces KA-induced neurodegeneration in the CA1 region. These findings establish EmtinB as a promising target for therapeutic development.

U2 - 10.1002/jnr.22281

DO - 10.1002/jnr.22281

M3 - Journal article

C2 - 19937811

VL - 88

SP - 1074

EP - 1082

JO - Journal of Neuroscience Research

JF - Journal of Neuroscience Research

SN - 0360-4012

IS - 5

ER -